Adverum Biotechnologies (ADVM) Study Update summary

Study design and objectives

• LUNA Phase II trial evaluated Ixo-vec gene therapy in wet AMD patients, focusing on dose selection and corticosteroid prophylactic regimens for Phase III readiness.

• Multicenter, double-masked, randomized, parallel-group design with 60 participants split between 6E10 and 2E11 vg/eye doses.

• Patients had a mean of 10–10.1 prior annualized anti-VEGF injections and demonstrated response to prior therapy.

• The 26-week interim analysis included 58 of 60 randomized patients, with primary endpoint at one year and total study duration of two years.

• Primary endpoints included mean change in BCVA and incidence/severity of adverse events through 52 weeks.

Efficacy results

• At 26 weeks, 76% (6E10) and 83% (2E11) of patients were injection-free, with ≥90% reduction in annualized anti-VEGF injections at both doses.

• Visual acuity (BCVA) and central subfield thickness (CST) were maintained, with LS mean BCVA change at week 26 of -1.1 (6E10) and -2.2 (2E11) letters.

• Greater CST reduction was observed in patients with baseline CST >300 μm.

• In the subgroup with fewer prior injections, 90% were injection-free at 26 weeks.

• Efficacy was consistent with prior OPTIC data, where 53% remained injection-free at three years.

Safety and prophylaxis findings

• Ixo-vec was well tolerated at both doses, with no related serious adverse events; all related AEs were mild or moderate, mainly dose-dependent anterior inflammation responsive to local corticosteroids.

• Enhanced local corticosteroid prophylaxis (difluprednate) minimized inflammation, with over 90% of patients experiencing no or minimal inflammation at week 26.

• Oral prednisone and OZURDEX implant did not add benefit over local steroids; topical difluprednate alone was effective.

• No cases of episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion, or hypotony were reported.

• No meaningful intraocular pressure fluctuations were observed post-dosing.